JPS62185170A - Apparatus and method for reading specimen information - Google Patents

Abstract

PURPOSE:To attain to enhance the reliability to the analytical result of information, by reading specimen information over the entire area of an accumulative phosphor sheet by an array type beam source. CONSTITUTION:The exciting beam from each beam source of an array type beam source 1 is projected to an accumulative phosphor sheet 5, on which a nucleic acid or protein specimen labelled with a radioactive marker was separated and developed, through a lens 3. The fluorescence from an exhaustive phosphor due to the projection of exciting beam is received by a photomultiplier tube 12 and photoelectrically converted to read specimen information. Subsequently, the exciting beam projecting position on the sheet 5 and a reading optical system 11 are moved to an X-direction and a Y-direction to perform the reading and scanning of specimen information continuously. By this reading and scanning of specimen information over the entire area of the sheet 5, the reliability to the analytical result of information can be enhanced.

Description

Detailed Description of the Invention [Technical Field] The present invention utilizes autoradiography to analyze samples such as deoxyliponucleic acid (DNA) and ribonucleic acid (RNA).
The present invention relates to a sample information reading device and a sample information reading method for reading information such as base sequences of proteins and amino acid sequences of proteins.

<Prior art and its problems> In molecular biology, which has developed rapidly in recent years, it is essential to clarify the genetic information of living organisms in order to elucidate their functions and replication mechanisms. It is said that In particular, salts of nucleic acids such as DNA (or DNA fragments or synthetic products, hereinafter referred to as such) carrying specific genetic information7. It has become essential to determine the H sequence or the amino acid sequence of a protein. Autoradiography is known as one of the methods.

By using this eid radiography, DN
As a method for determining the base sequence of A, etc., Sanger
The Sanger-Oulson method and the Maxam-Gilbert method
) law, is known. These methods are based on DNA having a double helical structure I + L, and the bond between two 30-shaped molecules forming the double helix, or the structure I of that molecule.
Attributable to hydrogen bonding between multiple bases at the p-position;
The IP-position of many of its constituent bases is adenine (A
), guanine (G), cytosine (C) and thymine (r
) consists of only four types of bases, and each constituent base? P-
By cleverly utilizing the characteristic structure of DNA in which hydrogen bonds between positions are realized only in two types of combinations, G-C and A-T, the salt J1 (method for determining the sequence It is.

Among the methods described in Section 2, the Sankar-Courlin method will be explained as a representative example.

In the Sanger-Kurusin method, there are several methods for synthesizing NA fragments that are complementary to the sample DNA whose base sequence is to be determined, but basically one strand of true sample DNA is used as a template (template). ), and DNA fragments of various lengths complementary to the sample DNA are synthesized by allowing a DNA synthesizing enzyme (DNA polymerase) to act in the presence of a mononucleotide triphosphate containing the above four types of bases. At this time, a radioactively labeled synthetic NA fragment (DNA composite) can be obtained by using a radioactively labeled mononucleotide triphosphate at the -.

Next, the mixture consisting of a large number of synthetic NA fragments obtained by this operation is separated and developed on a support medium by gel electrophoresis. By performing an autoradiography operation on this support medium, an autoradiograph of the isolated IJ (sequence) in which the synthetic NA fragments are separated and expanded is obtained. In this way, all salts of the sample DNA (J, II) can be sequenced (sequenced).
The sequence of , can be determined.

Further, detailed descriptions of the characteristics and operation of the Sanger-Kurusin method as specified in -1- can be found in the following literature.

rReading genetic information in its original language - Surprising salt of DNA J,
(Sequence analysis method 1, Kinichi Miura, Gendai Kagaku, September 1977 issue 46-54 > 1 (-Tokyo Kagaku Dojindan)) In this way, autoradiography can be used to analyze DNA information, similar to DNA base sequencing. When applied to reading analysis,
Conventionally, there have been the following problems.

The gel membrane, which serves as a support medium for separating and developing sample DNA, was handmade by each researcher, so not only did it take a lot of time and complicated work to create the gel membrane, but the gel membrane that was created was not homogeneous. However, as a result, the results of reading and analyzing the information on the sample DNA lacked reliability.

In addition, X-ray films have been used to expose these hand-made gel films, which require darkroom operation, long exposures at low temperatures, wet processing, chemical and/or physical There were many problems that needed to be resolved, including fogging.

In order to solve many of the problems mentioned above, we have developed a D
A method for determining the base sequence of NA (see Japanese Patent Application No. 58-201231, etc.) has been proposed by the applicant of the present application.

In this DNA base sequencing method, sample DNA with a radioactive label is transferred to a support medium (gel membrane) by electrophoresis, etc.
The support medium and a stimulable phosphor sheet having a stimulable phosphor layer are opened at a certain time, and the sheet carries a radiation image of the salt J1 (sequence) of the sample DNA. Excitation light is projected onto this sheet to cause the sheet to emit stimulated light, which is then received to read and analyze DNA uA group sequence information.

A DNA information reading device for reading DNA information from such a stimulable phosphor sheet is a laser, etc.
- the excitation light emitted from the light source is deflected by 10 stages of excitation light polarization such as a polygon mirror or a galvanometer mirror,
This scans a stimulable phosphor sheet.

Historically, in order to refine the structure of the reader, a latent image on a stimulable phosphor sheet was detected using an array light source in which multiple tiny light sources (light emitting elements such as light emitting diodes) were arranged in rows. is also being considered.

The excitation light emitted from this array light source passes through an optical system and images minute light spots on the stimulable phosphor, but gaps are created between the minute light spots and no reading is performed on these spots. Therefore, in order to read information without gaps, the light emitting elements Y- of the array light source must be closely arranged.

However, when a large number of light emitting elements are closely arranged, a lot of heat is generated from those light emitting elements, making it difficult to increase the light emitting output, and having an adverse effect on equipment etc. When using such an array light source, a small gap is provided between the light emitting elements arranged in the array. Therefore, in a reading method using an array light source, a discrete wave of 14
All I could do was read it.

There is also a sample information reading device that has a configuration in which a single light source is moved relative to a light sheet by an accumulative property 11 to read and scan sample information over the entire sheet area.

However, with this device, in order to scan the entire sheet,
There are drawbacks such as the number of times the sheet or the light source goes back and forth, the number of times the sheet or light source needs to be reciprocated, the υ control requires one person, and the device becomes expensive and expensive.Therefore, as a result of intensive research, the inventors of the present application found that Even when using an array light source, it is possible to read information over almost the entire area of the stimulable phosphor sheet, making it possible to read information over almost the entire area of the stimulable phosphor sheet.
, j, and a specimen information reading device and method that both shorten the reading time and led to the present invention.

<Linary aspect of the invention> The purpose of the present invention is to solve the above-mentioned problems in reading information on specimens such as DNA, RNA, and proteins, and especially on information on specimen DNA sequences, and to Even when a light source is used, it is possible to detect a latent image over the entire area of the stimulable phosphor sheet in a short time, and the structure of the device is simple and the sample information can be read to a small value. The present invention aims to provide an apparatus and a specimen++1iffi reading method.

<Simplified explanation of the invention> The above object is achieved by the present invention described in (1).

That is, the present invention provides an array light source in which a plurality of light sources that emit excitation light are arranged at regular intervals, and a method for separating radioactively labeled nucleic acids or proteins (hereinafter collectively referred to as "analytes"). a stimulable phosphor sheet that covers a stimulable phosphor layer carrying a radiation image of tj4 J, cy sequence or amino acid sequence information 11 constituting at least one analyte on the hζ-opened support medium; , a means for projecting excitation light from an array light source described in +frf onto the stimulable phosphor sheet; and a means for reading sample information by applying E(E) to almost the entire area of the stimulable phosphor sheet while synchronously projecting excitation light from the array light source and receiving stimulated luminescence by the photoelectric conversion means. drive means for moving the arrayed light source and/or 1) η excitation light projecting means relative to the stimulable phosphor sheet 111; a control means for controlling the driving means to read and scan the information in a desired order.

Furthermore, the present invention provides a method for converting excitation light emitted from each light source of an array light source in which a plurality of light sources are arranged at regular intervals into radioactively labeled tJ-labeled nucleic acids or proteins (hereinafter collectively referred to as "analyte"). A stimulable phosphor layer carrying a radiation image of a sequence of base sequences or amino acid sequences constituting at least one kind of analyte on a separated support medium is applied to a stimulable phosphor sheet. The excitation light is projected through the excitation light projection means, and the stimulated luminescence from the stimulable phosphor is received by the excitation light projection, photoelectrically converted, and sample information is read. The array light source and/or the excitation light projection plate is moved 1"Iη relative to the sheet so that the excitation light is emitted and received again in the part where the excitation light was not emitted. This specimen information reading method is characterized in that the specimen information in the marked portion is read, and this operation is sequentially repeated (1) to read the specimen information over almost the entire area of the stimulable phosphor sheet.

In both of the above inventions, the array light source of the specimen ++7ffl reading device may be a light emitting diode or a lower conductor laser.

The excitation light projected onto the stimulable phosphor sheet from the array light source may be light in a wavelength range that does not substantially include the stimulated emission wavelength range of the stimulable phosphor.

The photoelectric conversion means is preferably a photomultiplier tube.

Preferably, the tl control means is a computer.

<Structure of the Invention> Hereinafter, preferred embodiments of the specimen information reading device and specimen information reading method of the present invention will be described in detail as shown in the accompanying drawings.

FIG. 1 is a perspective view showing the structure of the sample information reading device of the present invention. The sample information reading device includes the following components.

Note that in FIG. 1, the driving means and its control means, which will be explained below in F, are omitted.

(a) An array light source in which a plurality of light sources that emit excitation light are arranged at regular intervals.

(b) At least one sample of nucleic acid or protein (analyte) to which a radioactive label has been added is separated and developed on a support medium.
A stimulable phosphor sheet with a phosphor layer that carries a radiation image of an information sequence of a base sequence or an amino acid sequence constituting a species specimen.

(c) A means for projecting excitation light onto the stimulable phosphor sheet from an array light source.

(d) A means for receiving and photoelectrically converting stimulated luminescence from a stimulable phosphor by projecting excitation light.

(e) Accumulation while emitting excitation light from the array light source and receiving stimulated light emission by the photoelectric conversion means) 1°
Drive ``1 step'' to move the array light source and/or the excitation light projection F step relative to the sheet so as to read specimen information over almost the entire area of the i-type phosphor sheet.

(f) Specimen of HI-1 fluorescent substance GET ++i fbi
control means for controlling said drive means to read and operate the columns in a desired order;

The constituent elements described below will be explained in detail below.

(1) Array light source As shown in FIG. 2, the array light source 1 has a structure in which a plurality of light emitting elements 2 are arranged in a row on a substrate.

The light emitting element 2 may be any element as long as it has the property of causing the stimulable phosphor of the spaced phosphor sheet 5 to stimulate luminescence when the stimulable phosphor sheet 5 described below is irradiated with excitation light. Preferably, a high brightness light emitting diode (LED) or a semiconductor laser is used.

Such light emitting elements 7-2 are arranged at regular intervals as shown in FIG.

It is preferable that the emission wavelength of the stimulable phosphor and the wavelength of the excitation light do not overlap.For example, the emission range of the stimulable phosphor is about 300 to 500 nm, whereas the excitation light emitted from the array light source l is The wavelength is 550-85001.

Each light emitting element 2 of the array light source 1 used in the present invention emits light independently of each other. For example, each light emitting element is connected to an independent circuit, and the array light source 1 is controlled by switching selection. It can be configured to repeatedly turn on and off sequentially from one end.

The light emission intensity of the valley light emitting element 2 is preferably controlled appropriately so that the light of the valley minute light spot imaged on the stimulable phosphor sheet 5 through the lens system 3, which will be described later, is equal. This allows information to be read uniformly over the entire surface of the phosphor sheet.

For such an array light source 1, for example, the following commercially available products can be used after being modified for the present invention.

LED array BU4265-A4R type specifications manufactured by Stanley ■ Emission center wavelength: 660 nm Light emitting element pitch: 2.5 mm Light emitting element r-size: Approximately 33#m Total number of light emitting elements = 96 Light emitting output: Approximately 1 mW/piece Such an array Since the light source, especially the commercially available product, is small and compact, it can contribute to miniaturization of the specimen +11i information reading device.

Furthermore, an array light source can be formed by arranging conductor lasers in an array. An example of an L conductor laser suitable for this 1-1 is the LTO manufactured by Sharp.
There is 24MD. The output wavelength is 780 nm and the emission output is 20 mW.

(2) Support medium The support medium is used to separate a sample such as a radioactively labeled sample DNA by electrophoresis or the like.

Previously, each research project had created an L-shaped support medium with gel interposed between glass plates, but it took a very long time to produce the gel plates, and the quality of the gel plates varied, so it was difficult to solve this problem. There were also problems with the reliability of the DNA analysis information used.

For this reason, the supply of standardized Kel membranes is desperately needed and
1: Development is progressing well with photographic film ■.

Although there are various configurations of gel membranes, the basic structure is shown in FIG. As shown in the figure, the supporting medium (gel film) 4 has a gel layer 7 preferably made of polyacrylamide interposed between a pair of transparent plates 6 facing each other, and these are separated by side spacers 9.
It has an integrated structure. A plurality of slots (cutouts) 8 (four in the drawing) are provided at one end of the gel layer 7.
is formed, and the specimen is configured to be able to be appropriately injected into the slot 8 using a pipette or the like.

Note that the support medium is not limited to the structure shown in FIG. 3, and includes, for example, a gradient end gel membrane in which the electrophoresis direction of the gel layer is provided with a J′y taste surface distribution slope, or a support medium with a diagonal row of sample migration columns. A gel film with a structure in which partition walls are provided between transparent substrates to prevent meandering and meandering, and the gel layer is divided into multiple lanes (patent application published in 1986)
0-232191 by the applicant) can be used.

Injecting a specimen into each slot 8 of such a support medium 4,
When electrodes are attached to both ends of the support medium 4 and a voltage is applied, the sample undergoes electrophoresis gradually through the slot 8, and is separated and developed in the gel layer.

The rods '1' at both ends are often formed by contact between both end surfaces of the gel layer 7 and the electrophoresis buffer solution.

Is this separated and expanded specimen information string as described later? The image is transferred to the trilaminar phosphor sheet 5 as an accumulated image of radiation energy, and the sheet to which this sample information sequence is transferred is subjected to reading. Therefore, in the following explanation, in order to make it easy to understand, the direction of electrophoresis is assumed to be the X direction, and the direction of slot arrangement perpendicular to this is assumed to be the Y direction, as shown in FIGS. 1, 3, and 4. This will be explained as a direction.

The support medium is most preferably the gel membrane for electrophoresis described above, but is not limited thereto, and any support medium that can separate and develop the specimen, such as a chromatograph, may be used.

(3) Stimulable phosphor sheet One of the features of the present invention is that a stimulable phosphor sheet 5 is used instead of a radiation-sensitive film, and the stimulable phosphor sheet used is also called a radiation image conversion panel. For example, Japanese Patent Application Laid-Open No. 55-121
It is described in Japanese Patent Application No. 45, Japanese Patent Application No. 57-193418, etc., and the general structure is already known, so a detailed explanation will be omitted.

That is, the stimulable phosphor sheet has a stimulable phosphor layer, and the stimulable phosphor of the sheet absorbs the radiation energy that has passed through the subject or the radiation energy that has been emitted from the subject. Later, by exciting the sheet using electromagnetic waves (excitation light) in the visible or infrared region, the radiation energy accumulated in the stimulable phosphor of the sheet is released as fluorescence (stimulated luminescence). It is something that can be done. Therefore, a radiation image of a subject or subject is obtained by photoelectrically reading this fluorescence and converting it into an electrical signal. It can be reproduced as , or expressed as numerical or symbolic position information.

Autoradiography is used to obtain positional information regarding a sample of a radiolabeled substance separated and developed on support medium-F. ! ! By exposing the developed specimen to light by aligning the support medium (gel film) 4 and the stimulable phosphor sheet 5 for a certain period of time, radiation emitted from the radiolabeled substance on the support medium is detected. The sample information on the support medium is transferred to the sheet 5 by absorbing at least a portion of the sample information onto the sheet 5.

In the exposure operation, the state in which the gel layer 7 of the support medium 4 and the stimulable phosphor sheet 5 are brought together as described in -1- is usually achieved by bringing the stimulable phosphor sheet 5 into close contact with the gel layer 7, but it is not always necessary. It is not necessary that the gel layer 7 of the support medium 4 and the stimulable phosphor sheet 5 be in close contact with each other, and they may be placed in close proximity. Furthermore, the gel layer 7 does not necessarily need to be in a dry state; it may be in a moist state, or if desired, it may be wrapped in a thin polyester film or the like having a thickness that does not interfere with radiation from radioactively labeled DNA fragments. Good too.

In addition, the so-called exposure time is the radiation intensity from the radioactively labeled biological substance contained in the gel layer 7, the:1 knee of the substance 71,
Although it varies depending on the sensitivity of the stimulable phosphor sheet 5 and the positional relationship between the support medium 4 and the stimulable phosphor sheet 5,
The exposure operation requires a certain period of time, for example, several seconds or more. However, by using the stimulable phosphor sheet 5 as the photosensitive material, the exposure time is significantly shortened compared to the exposure time required when using a conventional X-ray film. In addition, in the operation of reading the positional information of the radiolabeled substance in the gel layer 7 accumulated and recorded on the stimulable phosphor sheet from the gel layer 7 of the support medium 4 by exposure, the intensity of the energy accumulated in the sheet is For example, by performing electrical processing of extrapolation according to the distribution, desired information, etc., 11? Strict control of the exposure time during exposure operations is especially necessary because it is important to appropriately process the obtained position information, such as being able to set the amplification factor of the streetcar signal to an arbitrary value. I don't.

Further, although there is no particular restriction on the temperature at which the exposure operation is performed, autoradiography using the stimulable phosphor sheet 5 of the present invention can be performed at an environmental temperature of about 10 to 35°C. be. However, it is also possible to carry out the exposure operation at a low temperature (eg, around 5° C. or lower), which is used in conventional autoradiography using an X-ray film.

The stimulable phosphor sheet 5 suitably used in the above autoradiography generally has a basic structure of J,
(It consists of a plate and a phosphor layer made of a binder that supports the stimulable phosphor provided on this substrate in a dispersed state. However, if the phosphor layer is given self-supporting property, teeth,
It is not necessarily necessary to provide a substrate.

As a substrate, any material can be selected from the various materials used as supports for intensifying screens (or fluorescent intensifying screens) in the conventional radiography 1'' method. Examples of such materials are: Examples include films of plastic materials such as cellulose acedate and polyethylene terephthalate, metal sheets such as aluminum foil, ordinary paper, baryta paper, resin-coated paper, and the like.

In addition, the surface of the substrate on which the phosphor layer is provided has adhesive properties! j1 layer, a light reflection layer, a light absorption layer, etc. may be provided.

In the present invention, it is convenient to use a standardized stimulable phosphor sheet as well as the support medium. Such a standardized material facilitates alignment of both when setting it in the sample information reading or analysis device of the present invention or when exposing at another location, and also facilitates setting of the reading sequence at the time of reading. It also has excellent compatibility with the device of the invention.

The stimulable phosphor used in the stimulable phosphor sheet used in the present invention is a phosphor that exhibits stimulated luminescence when irradiated with radiation and then irradiated with excitation light, as described above. From a practical point of view, it is desirable that the fluorophore exhibit stimulated luminescence in the wavelength range of 300 to 500 nm by excitation light in the wavelength range of 550 to 850 nm. Examples of such stimulable phosphors include U.S. Pat. No. 3,859,52
No. 7 specification i+7, JP-A-55-12142, same 5
No. 5-12143, No. 55-12144, No. 55-12145, No. 55-160078, No. 56-116777, No. 57-236
Publication No. 73, Publication No. 57-23675 fN, Patent Application No. 1983
-167498 specification-), 57-s 9 a 7
5 s) Four sets of one fortune, No. 57-137374 specification-2,
1ii157-158048 specification, 1F, 57-1
Typical examples include those described in No. 66320 Specification, 1), No. 57-166696 Gin Specification-7, and No. 57-ta44sss Specification J).

Such ii stacked phosphor sheets 5 and stimulable phosphor sheets 5 and support medium 4 (gel film) as the case may be are appropriately positioned for exposure or information reading in the sample information reading device of the present invention. There is a need. Therefore, in the apparatus of the present invention, it is preferable to provide a mounting table 14 on which the storage h1P [phosphor sheet 5 or the same sheet 5 and the support medium 4 is placed.

When placing the sheet 5 or the support medium 4 on the mounting table 14, it would be good to be able to position either of them at a predetermined position on the table. This facilitates exposure or reading. As the positioning means on the mounting table 14, any single stage may be used as long as the positioning can be performed, but it is preferable to attach a mark on the mounting table 14 because it is simple. Other than this, a stop or claw can also be used.

(4) Excitation light projection "1 stage + irr emitted from the array light source 1" - the excitation light is:
A minute light spot is imaged on the stimulable phosphor sheet 5 by one stage of excitation light projection from a lens system 3 or the like.

One or several types of optical lenses are used as one stage of excitation light projection,
It is composed of various filters and the like, and if it is capable of forming an image of a minute light spot of the size necessary for the storage i, +t++1 phosphor sheet 51-, then IE, f5, etc., are suitable for the whites of the eyes.

FIG. 2 shows a state in which excitation light is projected onto the stimulable phosphor sheet 5 by the excitation light projection means.

The excitation light emitted from the light emitting elements 2 of the array light source 1 is
An image is formed on the stimulable phosphor sheet 5F by the action of the lens system 3, creating a minute light spot.

When this excitation light includes a part of the stimulated emission wavelength region, it is preferable to close the filter 10 and cut out the light in the stimulated emission wavelength region in order to read information accurately. .

The size, intensity, pitch, etc. of the minute light spots imaged on the stimulable phosphor sheet 5 are appropriately determined as necessary.

Therefore, the excitation light projecting means may be selected or adjusted to satisfy the above conditions.

For example, a case will be discussed in which light is projected onto a stimulable phosphor sheet by forming an image at a same magnification. As shown in FIG. 2, a lens f-3 having an appropriate focal length is installed between the array light source 1 and the stimulable phosphor sheet 5 to project light. Since the minute light spots on the stimulable phosphor sheet 5F are imaged at the same magnification, the size of the minute light spots is approximately equal to the size of the light emitting elements 2, and the pitch of the minute light spots is also equal to the installation interval of the light emitting elements 2. becomes.

The present invention is applicable not only to the case of L equal magnification imaging but also to lenses, f-3
The magnification etc. can be freely selected by selecting .

It should be noted that the lens may be one that can project excitation light over almost the entire YH direction of the stimulable phosphor sheet 5, and it is preferable to use a convex lens with a large [-1] diameter because it can easily cover a wide range.

The excitation light projecting means in conventional specimen (DNA) information reading devices using light sources is a complex system that combines lens systems, filters, prisms, mirrors (galvanometer mirrors, polygon mirrors), etc. Moreover, since a driving means for relatively moving these parts is required for scanning, the reading apparatus tends to become larger and more complicated. However, in the sample information reading device of the present invention, since the system of the excitation light projection stage is simple as described above, the device can be downsized.

Note that, as mentioned above, since the array light sources 1 are arranged at regular intervals, minute light spots are also formed on the stimulable phosphor sheet 5F at regular intervals. Therefore, the array light source, the excitation light projection means, the photoelectric conversion means, and the stimulable phosphor sheet 5 are moved relative to each other by the driving means described later, and the excitation light is projected so as to fill the gaps between the minute light spots. , reads information.

(5) One-stage photoelectric conversion plate The sample information reading device of the present invention, as shown in FIG. 1, has means 11 for receiving stimulated luminescence from a stimulable phosphor using excitation light and photoelectrically converting it. .

The photoelectric conversion means 11 may be of any type as long as it receives stimulated luminescence from the stimulable phosphor caused by excitation light projected onto the phosphor sheet 5 and exchanges it into an electrical signal. Typical examples include a phototube and a photomultiplier tube, but it is preferable to use a photomultiplier tube 12 that has a high signal amplification ability.

The photomultiplier tube 12 is equipped with a light guide sheet 13 for guiding stimulated luminescence to the light receiving surface of the photomultiplier tube 12 .

The light guiding sheet 13 has a linear incident surface at one end, and the other 5;
An annular exit surface is formed on the photomultiplier tube 12.
is connected to the light receiving surface. Note that the length of the linear incident surface is
The length should be long enough to cover the entire effective length of the array light source, preferably about the effective scanning width of the stimulable phosphor sheet 5.

This light guide sheet 13 is made by processing a transparent thermoplastic resin sheet such as acrylic synthetic resin, and the stimulated light incident from the incident surface is totally reflected inside the light guide sheet 13 and directed to the exit surface. It is structured so that it can be transmitted. Stimulated luminescence from the phosphor sheet 5 is guided through the light-guiding sheet 13 and reaches the exit surface, is emitted from the exit surface, and is received by the γ multiplier 12 at 9'1.

In addition, 4 YP [preferred shape of sheet, moon? The first class is disclosed in Japanese Patent Application Laid-open No. 55-87970, Japanese Patent Application Laid-open No. 56-11397, etc.

(6) Drive plate/stage? In order to read sample information over the entire area of the phosphor sheet 5, it is necessary to move the position on the phosphor sheet 5 where the excitation light is projected in the X and Y directions. is necessary.

Therefore, 1 the device of the present invention uses the drive means to project the excitation light and receive the stimulated luminescence synchronously, while directing the array light source 1 and/or the excitation light projecting means to the stimulable phosphor sheet 5. It is configured to move relatively in the X direction and the Y direction.

Hereinafter, this relative movement pattern will be explained separately in the X direction and the Y direction.

<X direction> ■ When moving the array light source 1, one stage of excitation light projection, and the photoelectric conversion means 11■ When moving the stimulable phosphor sheet 5■ -Note■
A combination of and ■ is possible.

■ When moving the array light source 1 ■ When moving the excitation light projection stage ■ When moving the array light source 1 and the excitation light projection means ■ When moving the array light source 1 and the photoelectric conversion means Case■ When moving the excitation light projection stage and photoelectric conversion means■ Array light source 1, excitation light projection means, and photoelectric conversion p
When moving the stage 11■ When moving the stimulable phosphor sheet 5■ 1.■～
It is possible to combine one of (I) and (2).

The object that moves relative to the stimulable phosphor sheet 5 will be collectively referred to as a "reading optical system" in the following description.

Any type of one-stage drive mechanism for moving the reading optical system and the sheet 5 may be used, such as a servo motor, a stepping motor, or a sliding mechanism using a rack, pinion gear, wire, etc. A known technique may be applied.

Furthermore, the mode of movement may be continuous movement or intermittent movement in both the X and Y directions, but in the Y direction, the light is projected so as to fill the gap between the minute light spots imaged on the phosphor sheet 5 lx. "Need to perform"-1 It is preferable to configure the system to move intermittently.

(7) Il control means The specimen information reading device of the present invention includes a control means that can control a series of operations from the start to the end r of reading and scanning the specimen information string of the stimulable phosphor sheet 5. I'll do it.

Preferably, such I+ control means is constituted by a computer, and the computer is preferably provided with a manual input stage for control-related information and an output means for command signals.

The first stage of control is the stimulable phosphor sheet 5 driven by the aforementioned driving means.
In addition to controlling the order, amount of movement, timing, etc. of the relative movement of the reading optical system in the X and Y directions, it can also control ON/OFF of each light emitting element of the array light source 1.

Further, in the sample information reading device of the present invention, in addition to the control means, it is also possible to have an analysis stage for analyzing the read sample information.

A specimen information reading method using the specimen information reading device having such a configuration will be described.

(1) A sample to which a radioactive label has been added is injected into the bowl slot 8 of the support medium 4 shown in FIG. 3 at an appropriate point i1 using a pipette or the like, and the sample is subjected to electrophoresis in the X direction. Since the electrophoresis speed of the specimen varies depending on its molecular weight, separation is performed in each slot in the gel layer 7.

In this way, the specimen is separated and developed and stored in the support medium 44.
A 1H phosphor sheet 5 is attached, and a radiation image is recorded by exposure. At this time, it is preferable to remove the transparent plate 6 from the support medium 4 and bring the stimulable phosphor sheet 5 into contact with the gel layer 7 directly or through a thin film to perform exposure recording.

Note that exposure recording on the stimulable phosphor sheet 5 is preferably carried out by fixing the sheet at a predetermined position on the mounting table 14 and placing the support medium 4 thereon, as positioning becomes easier.

After the exposure recording on the stimulable phosphor sheet 5 is completed, the support medium 4 is removed from the sheet 5.

(2) Perform an operation to read the specimen information on the stimulable phosphor sheet S.

As shown in FIG. 2, the excitation light emitted from the light emitting element T-2 of the array light source 1 is transmitted to the stimulable phosphor sheet by an excitation light projection stage composed of a lens system 3, a filter 10, etc. A minute light spot is imaged on 5.

When this minute light spot is irradiated to a predetermined position on the phosphor sheet 5, the stimulable phosphor in the phosphor sheet 5 is excited, and the energy stored in the phosphor is released as stimulated luminescence. .

As shown in FIG. 1, this stimulated luminescence enters the light-guiding sheet 13 from the linear incident surface, exits from the annular exit surface, and enters the photomultiplier tube 12 connected to the light-guiding sheet exit surface. Light is received. The photomultiplier tube 12 converts the received light into an electrical signal depending on its intensity.

(3) The projection of excitation light and the reception of stimulated luminescence in (2) are performed over almost the entire area of the stimulable phosphor sheet 5. A preferred example of the scanning method will be described below with reference to FIG.

FIG. 4 is a diagram showing changes over time in the positions of minute light spots formed by excitation light from the light emitting elements A, B, C, . . . on the stimulable phosphor sheet 5k. A1~AIO.

81~BIO, C1~Cl11. ...indicates a minute light spot.

The size of each minute light spot is approximately 0. :l×0.3mm. When the pitch of the light emitting elements T-2 arranged in the array light source 1 is 2.5 mm and the light is projected with equal magnification imaging, the pitch of the minute light spots A, , B, , C, . . . It will be about 2.5 mm.

The relative movement between the stimulable phosphor sheet 5 and the reading optical system is as follows:
In the case described below, it is assumed that the reading optical system is fixed in both the X direction and the Y direction, and the stimulable phosphor sheet 5 is moved. Note that these conditional limitations are made for convenience of explanation, and the content of the present invention is not limited thereto.

(2) Continuously move the stimulable phosphor sheet 5 from the starting point in the X direction (at a speed of 3 cm/s) while the array light source 1
The light emitting elements 2 are sequentially turned on and off from one end to emit light in the order of minute light spots Al, B, C, . . . , and this process is repeated. Note that the reading speed in the Y direction is approximately 1 ms/1ine.

Each minute light spot A, B, C, .

II, a minute light spot is projected along the reading line ■,
After reaching the end point in the direction, the array light source 1 stops emitting light, returns the stimulable phosphor sheet to the X direction scanning start point, and moves 0.25 mm in the Y direction. Note that it is preferable to make the movement H,1 in the Y direction slightly smaller than the length of the minute light spot in the Y direction, since the stimulable phosphor sheet 5F can be scanned without gaps.

! 11. By performing the same operation as in (■) from state H, each minute light spot A2, B2, C2, . In this manner, FIG and reading are performed on the portions to which the excitation light is not projected during mechanical scanning.

■, After the reading scan of reading line ■ is completed, 11 "1
Steps II and (2) are repeated in sequence, and the pre-read scan is completed when the scan of the read line [phase] is completed.

By executing the reading method described above, specimen information can be read over the entire area of the stimulable phosphor sheet using the light emitting elements scattered in an array.

Note that on the foot side, only the stimulable phosphor sheet is moved in both the X and Y directions, but the reading optical system can also be moved in each direction to perform reading scanning, and in that case, the above steps can also be performed. It is preferable to set 1- so that reading and scanning are performed in the order of (2).

In these cases, the stimulable phosphor sheet or the reading optical system is moved 10 times in the X direction from the start of reading to the reading light r. M, and the entire surface of the h°1 phosphor sheet can be read and scanned in a short time.

<Effects of the Invention> According to the sample information reading device and the sample information reading method of the present invention, the stimulable phosphor sheet and the reading optical system can be positioned relative to each other in the Y direction while producing the advantages of using an array light source. By moving, reading scanning can be performed not only in the X direction but also in the Y direction without any gaps. Therefore, the specimen information can be read and scanned over almost the entire area of the stimulable phosphor sheet, and the reliability of the information analysis results is improved.

In the apparatus and method of the present invention, the number of reciprocations in the X direction can be reduced by using an array light source.

This is significantly reduced compared to scanning using a conventional single light source. As a result, the total distance traveled by the follower is shortened, making it possible to perform reading scans in a short time with simple control.

Furthermore, in the device of the present invention, since the light emitting elements of the array light source do not necessarily have to be closely arranged, heat generation can be suppressed and the durability of the device, especially the array light source, can be improved.

Further, since the device of the present invention has a simple structure as described above, the device can be made smaller and can be manufactured at low cost.

[Brief explanation of drawings]

FIG. 1 is a perspective view of the sample information reading device of the present invention. FIG. 2 is a side view showing the positional relationship and structure of the array light source, excitation light projection means, and stimulable phosphor sheet used in the present invention. FIG. 3 is a perspective view of a support medium used in the present invention. FIG. 4 is a plan view showing the scanning order of the stimulable phosphor sheet 7 in the present invention. Explanation of symbols! ...Array light source, 2...Light emitting element. 3... Lens system, 4... Support medium (Gel I+!2), 5... Stimulative phosphor sheet, 6... Transparent plate, 7... Gel layer, 8... Slot, 9... Side spacer, 10-... Filter, 11... Photoelectric conversion means, 12... Photoelectric f multiplier tube, 13-... Light guiding sheet, 14... Mounting table applicant Tori Minoru Watanabe, patent attorney and agent for Photo Film Co., Ltd. FIG, 1 FIG, 2 FIG, 3 FIG, 4

Claims (12)

[Claims] (1) An array light source in which multiple light sources that emit excitation light are arranged at regular intervals, and a support medium in which radioactively labeled nucleic acids or proteins (hereinafter collectively referred to as "analytes") are separated and developed. upper,
a stimulable phosphor sheet having a stimulable phosphor layer carrying a radiation image of an information sequence of a base sequence or an amino acid sequence constituting at least one analyte; means for projecting excitation light; means for receiving and photoelectrically converting stimulated luminescence from the stimulable phosphor by the projection of the excitation light; and projection of the excitation light from the array light source and the photoelectric conversion. The array light source and/or the excitation light projecting means are connected to the stimulable phosphor sheet so as to read specimen information over almost the entire area of the stimulable phosphor sheet while synchronously receiving stimulated luminescence by the means. The stimulable phosphor sheet is characterized by comprising a drive means for moving the sheet relatively to the sheet, and a control means for controlling the drive means so as to read and scan the analyte information array on the stimulable phosphor sheet in a desired order. Sample information reading device. (2) The specimen information reading device according to claim 1, wherein the array light source is a light emitting diode. (3) The specimen information reading device according to claim 1, wherein the array light source is a semiconductor laser. (4) The excitation light projected onto the stimulable phosphor sheet from the array light source is light in a wavelength range that does not substantially include the stimulated emission wavelength range of the stimulable phosphor. A sample information reading device according to any one of claims 1 to 3. (5) The specimen information reading device according to any one of claims 1 to 4, wherein the photoelectric conversion means is a photomultiplier tube. (6) The specimen information reading device according to any one of claims 1 to 5, wherein the control means is a computer. (7) Radioactively labeled nucleic acids or proteins (hereinafter collectively referred to as "analytes") are separated and developed using excitation light emitted from each light source of an array light source in which multiple light sources are arranged at regular intervals. The excitation light is projected via an excitation light projecting means onto a stimulable phosphor sheet having a stimulable phosphor layer carrying a radiation image of an information sequence of a base sequence or an amino acid sequence constituting at least one analyte on a support medium. After receiving the stimulated luminescence from the stimulable phosphor by projecting the excitation light and converting it into electricity and reading the sample information, the stimulable phosphor sheet is exposed to the part where the excitation light was not projected. By moving the array light source and/or the excitation light projecting means relative to the sheet so that light is emitted and received again, and reading the specimen information of the portion, and repeating this operation sequentially. A method for reading specimen information, comprising reading specimen information over almost the entire area of the stimulable phosphor sheet. (8) The specimen information reading method according to claim 7, wherein the array light source is a light emitting diode. (9) The specimen information reading method according to claim 7, wherein the array light source is a semiconductor laser. (10) The excitation light emitted from the array light source to the stimulable phosphor sheet is light in a wavelength range that does not substantially include the stimulated emission wavelength range of the stimulable phosphor. A method for reading specimen information according to any one of claims 7 to 9. (11) The specimen information reading method according to any one of claims 7 to 10, wherein the means for receiving and photoelectrically converting the stimulated luminescence is performed by a photomultiplier tube. (12) Relative movement of the array light source and/or the excitation light projecting means with respect to the stimulable phosphor sheet:
The specimen information reading method according to any one of claims 7 to 11, characterized in that the method is controlled by a computer-based control means.